Abstract
Background: Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats. Methods: Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method. Results: The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC<sub>(0-t)</sub>, AUC<sub>(0-</sub><sub>∞</sub><sub>)</sub>, t<sub>1/2</sub> and C<sub>max</sub> of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t<sub>1/2</sub>, CL and T<sub>max</sub> for phenacetin, tolbutamide and midazolam. Conclusions: A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks.
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